Fluid shear stress promotes proprotein convertase-dependent activation of MT1-MMP. Academic Article uri icon


  • During angiogenesis, endothelial cells (ECs(1)) initiate new blood vessel growth and invade into the extracellular matrix (ECM). Membrane type-1 matrix metalloproteinase (MT1-MMP) facilitates this process and translocates to the plasma membrane following activation to promote ECM cleavage. The N-terminal pro-domain within MT1-MMP must be processed for complete activity of the proteinase. This study investigated whether MT1-MMP activation was altered by sphingosine 1-phosphate (S1P) and wall shear stress (WSS), which combine to stimulate EC invasion in three dimensional (3D) collagen matrices. MT1-MMP was activated rapidly and completely by WSS but not S1P. Proprotein convertases (PCs) promoted MT1-MMP processing, prompting us to test whether WSS or S1P treatments increased PC activity. Like MT1-MMP, PC activity increased with WSS, while S1P had no effect. A pharmacological PC inhibitor completely blocked S1P- and WSS-induced EC invasion and MT1-MMP translocation to the plasma membrane. Further, a recombinant PC inhibitor reduced MT1-MMP activation and decreased lumen formation in invading ECs, a process known to be controlled by MT1-MMP. Thus, we conclude that PC and MT1-MMP activation are mechanosensitive events that are required for EC invasion into 3D collagen matrices.

published proceedings

  • Biochem Biophys Res Commun

author list (cited authors)

  • Kang, H., Duran, C. L., Abbey, C. A., Kaunas, R. R., & Bayless, K. J.

citation count

  • 15

complete list of authors

  • Kang, Hojin||Duran, Camille L||Abbey, Colette A||Kaunas, Roland R||Bayless, Kayla J

publication date

  • January 2015